Analysis of RIM Expression and Function at Mouse Photoreceptor Ribbon Synapses
Analysis of RIM Expression and Function at Mouse Photoreceptor Ribbon Synapses
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DOI：
10.1523/jneurosci.2795-16.2017
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发表时间：
2017-08-16
影响因子：
5.3
通讯作者：
Regus-Leidig, Hanna
中科院分区：
文献类型：
--
作者：
Loehner, Martina;Babai, Norbert;Regus-Leidig, Hanna
RAB 3A相互作用分子（RIM）蛋白是活性区释放递质的重要调节因子。在传统的化学突触，RIM大大有助于囊泡启动和对接，它们的损失减少了高达75%的突触囊泡容易释放池。RIMs的启动功能是通过与Munc 13和RAB 3A形成三方复合物介导的，该复合物使突触囊泡靠近Ca 2+通道和融合位点并激活Munc 13。我们以前报道，在小鼠感光带突触，囊泡启动是Munc 13独立的。在这项研究中，我们研究了RIM的表达，分布和功能，在男性和女性小鼠感光带突触。我们提供的证据表明，RIM 1 α和RIM 1 α很可能是缺乏小鼠光感受器和RIM 2 α是主要的大RIM亚型存在于感光带突触。我们发现，小鼠光感受器主要表达RIM 2变体，缺乏Munc 13的相互作用结构域。在RIM 2 α突变小鼠中全长RIM 2 α的缺失仅轻微干扰光感受器突触传递。因此，我们的发现有力地证明了感光带突触的启动机制独立于RIM-Munc 13-RAB 3 A复合物的形成，从而提供了进一步的证据
RAB3A-interacting molecule (RIM) proteins are important regulators of transmitter release from active zones. At conventional chemical synapses, RIMs contribute substantially to vesicle priming and docking and their loss reduces the readily releasable pool of synaptic vesicles by up to 75%. The priming function of RIMs is mediated via the formation of a tripartite complex with Munc13 and RAB3A, which brings synaptic vesicles in close proximity to Ca2+ channels and the fusion site and activates Munc13. We reported previously that, at mouse photoreceptor ribbon synapses, vesicle priming is Munc13 independent. In this study, we examined RIM expression, distribution, and function at male and female mouse photoreceptor ribbon synapses. We provide evidence that RIM1 alpha and RIM1 alpha are highly likely absent from mouse photoreceptors and that RIM2 alpha is the major large RIM isoform present at photoreceptor ribbon synapses. We show that mouse photoreceptors predominantly express RIM2 variants that lack the interaction domain for Munc13. Loss of full-length RIM2 alpha in a RIM2 alpha mutant mouse only marginally perturbs photoreceptor synaptic transmission. Our findings therefore strongly argue for a priming mechanism at the photoreceptor ribbon synapse that is independent of the formation of a RIM-Munc13-RAB3 A complex and thus provide further evidence